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https://www.readbyqxmd.com/read/28637278/functional-and-structural-analysis-of-at-specific-minor-groove-binders-that-disrupt-dna-protein-interactions-and-cause-disintegration-of-the-trypanosoma-brucei-kinetoplast
#1
Cinthia R Millan, Francisco J Acosta-Reyes, Laura Lagartera, Godwin U Ebiloma, Leandro Lemgruber, J Jonathan Nué Martínez, Núria Saperas, Christophe Dardonville, Harry P de Koning, J Lourdes Campos
Trypanosoma brucei, the causative agent of sleeping sickness (Human African Trypanosomiasis, HAT), contains a kinetoplast with the mitochondrial DNA (kDNA), comprising of >70% AT base pairs. This has prompted studies of drugs interacting with AT-rich DNA, such as the N-phenylbenzamide bis(2-aminoimidazoline) derivatives 1 [4-((4,5-dihydro-1H-imidazol-2-yl)amino)-N-(4-((4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)benzamide dihydrochloride] and 2 [N-(3-chloro-4-((4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)-4-((4,5-dihydro-1H-imidazol-2-yl)amino)benzamide] as potential drugs for HAT...
June 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28637228/application-of-social-network-analysis-in-the-assessment-of-organization-infrastructure-for-service-delivery-a-three-district-case-study-from-post-conflict-northern-uganda
#2
Freddie Ssengooba, Vincent Kawooya, Justine Namakula, Suzanne Fustukian
In post-conflict settings, service coverage indices are unlikely to be sustained if health systems are built on weak and unstable inter-organization networks-here referred to as infrastructure. The objective of this study was to assess the inter-organization infrastructure that supports the provision of selected health services in the reconstruction phase after conflict in northern Uganda. Applied social network analysis was used to establish the structure, size and function among organizations supporting the provision of (1) HIV treatment, (2) maternal delivery services and (3) workforce strengthening...
June 16, 2017: Health Policy and Planning
https://www.readbyqxmd.com/read/28637151/work-related-experiences-of-head-and-neck-cancer-survivors-an-exploratory-and-descriptive-qualitative-study
#3
Carolyn S Dewa, Lucy Trojanowski, Sietske J Tamminga, Jolie Ringash, Maurene McQuestion, Jeffrey S Hoch
PURPOSE: This exploratory and descriptive study contributes to the growing knowledge about the return-to-work (RTW) experience of head and neck cancer (HNC) survivors. Viewing RTW as a process, participants were asked to consider the work-related experience with HNC at different phases: (1) at diagnosis/pre-treatment, (2) working during treatment (if the respondent did not take a work disability leave), and (3) post-treatment/RTW (if the respondent took a work disability leave). METHODS: Data were gathered in nine individual semi-structured in-depth interviews with patients receiving treatment at a quaternary cancer center's HNC clinic in Ontario, Canada...
February 25, 2017: Disability and Rehabilitation
https://www.readbyqxmd.com/read/28637149/personal-meaning-in-relation-to-daily-functioning-of-a-patient-in-physical-therapy-practice-narratives-of-a-patient-a-family-member-and-physical-therapist
#4
Ellen Oosting, Jaap Dronkers, Thomas Hoogeboom, Nico van Meeteren, Willem Marie Speelman
PURPOSE: To get insight into personal meaning of a person involved in a physical therapy intervention. METHODS: Mrs. A, a 76-year-old woman is referred to a physical therapist (PT) for assessment of functioning and training before total hip arthroplasty (THA). The patient, her daughter, and PT were asked to write a story about their daily life. Stories were analyzed according to the narrative scheme based on a method to find meaning in daily life, which consists of four phases: 1...
February 24, 2017: Disability and Rehabilitation
https://www.readbyqxmd.com/read/28637005/cxcl13-is-androgen-responsive-and-involved-in-androgen-induced-prostate-cancer-cell-migration-and-invasion
#5
Long Fan, Qingyi Zhu, Li Liu, Cuicui Zhu, Haojie Huang, Shan Lu, Ping Liu
Androgen receptor (AR) is a key transcription factor playing a critical role in prostate cancer (PCa) initiation and progression. However, the molecular mechanisms of AR action in prostate cancer are not very clear. CXCL13, known as B cell attracting chemokine1 (BCA-1), is a member of CXC chemokine family and relevant to cancer metastasis. This study shows that CXCL13 is an androgen-responsive gene and involved in AR-induced PCa cell migration and invasion. In clinical specimens, expression of CXCL13 in PCa tissues is markedly higher than that in adjacent normal tissues...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636984/whether-low-dose-metronomic-oral-cyclophosphamide-improves-the-response-to-docetaxel-in-first-line-treatment-of-non-triple-negative-metastatic-breast-cancer
#6
Jian Zhang, Leiping Wang, Zhonghua Wang, Biyun Wang, Jun Cao, Fangfang Lv, Sheng Zhang, Zhimin Shao, Xichun Hu
Oral metronomic chemotherapy may target tumor cells indirectly via antiangiogenic activity, restoration of anticancer immune response, or induction of tumor dormancy. We initiated the single-center, randomized, open-label, phase II study to determine whether the addition of metronomic cyclophosphamide to docetaxel (T) (w/o trastuzumab) improves overall response rate (ORR) as first-line treatment among patients with non-triple-negative metastatic breast cancer (MBC). Eligible patients with previously untreated non-triple-negative MBC were randomly assigned (1:1) to receive 3-weekly cycles of Metro-TC (T 75mg/m2, d1 plus oral cyclophosphamide 50 mg daily) or T alone...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636883/the-effects-of-monocular-training-on-binocular-functions-in-anisometropic-amblyopia
#7
Wuli Jia, Fangfang Lan, Zhao Xin, Zhong-Lin Lu, Chang-Bing Huang, Wuxiao Zhao, Min Li
PURPOSE: It's been shown that intensive monocular perceptual learning can improve visual acuity, contrast sensitivity, and vernier acuity in the amblyopic eye in adults with amblyopia. It is however not clear how much monocular training can enhance binocular visual functions. In the current study, we aimed to evaluate effects of monocular training on a variety of binocular functions. METHODS: Nineteen anisometropic amblyopes (18.5±1.26 yrs) were trained in a grating contrast detection task near each individual's cutoff spatial frequency for 6 to 10 days (630 trials/day)...
June 18, 2017: Vision Research
https://www.readbyqxmd.com/read/28636851/first-line-nivolumab-in-stage-iv-or-recurrent-non-small-cell-lung-cancer
#8
David P Carbone, Martin Reck, Luis Paz-Ares, Benjamin Creelan, Leora Horn, Martin Steins, Enriqueta Felip, Michel M van den Heuvel, Tudor-Eliade Ciuleanu, Firas Badin, Neal Ready, T Jeroen N Hiltermann, Suresh Nair, Rosalyn Juergens, Solange Peters, Elisa Minenza, John M Wrangle, Delvys Rodriguez-Abreu, Hossein Borghaei, George R Blumenschein, Liza C Villaruz, Libor Havel, Jana Krejci, Jesus Corral Jaime, Han Chang, William J Geese, Prabhu Bhagavatheeswaran, Allen C Chen, Mark A Socinski
Background Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1 (PD-L1)-positive NSCLC. Methods We randomly assigned, in a 1:1 ratio, patients with untreated stage IV or recurrent NSCLC and a PD-L1 tumor-expression level of 1% or more to receive nivolumab (administered intravenously at a dose of 3 mg per kilogram of body weight once every 2 weeks) or platinum-based chemotherapy (administered once every 3 weeks for up to six cycles)...
June 22, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28636818/critical-temperature-of-1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine-monolayers-and-its-possible-biological-relevance
#9
Jordi Hernandez Borrell, Oscar Domenech
Since transmembrane proteins (TMPs) can be obtained with sufficient purity for x-ray diffraction studies more frequently than decades ago, their mechanisms of action may now be elucidated. One of the pending issues is the actual interplay between transmembrane proteins and membrane lipids. There is strong evidence of the involvement of specific lipids with some membrane proteins, such as the potassium crystallographically sited activation channel (KcsA) of Streptomyces lividans and the secondary transporter of lactose LacY of Escherichia coli, the activities of which are associated with the presence of anionic phospholipids such as the phosphatidylglycerol (PG) and phosphatidyethanolamine (PE), respectively...
June 21, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28636677/contextual-imitation-of-intransitive-body-actions-in-a-beluga-whale-delphinapterus-leucas-a-do-as-other-does-study
#10
José Z Abramson, Mª Victoria Hernández-Lloreda, José-Antonio Esteban, Fernando Colmenares, Francisco Aboitiz, Josep Call
Cetaceans are remarkable for exhibiting group-specific behavioral traditions or cultures in several behavioral domains (e.g., calls, behavioral tactics), and the question of whether they can be acquired socially, for example through imitative processes, remains open. Here we used a "Do as other does" paradigm to experimentally study the ability of a beluga to imitate familiar intransitive (body-oriented) actions demonstrated by a conspecific. The participant was first trained to copy three familiar behaviors on command (training phase) and then was tested for her ability to generalize the learned "Do as the other does" command to a different set of three familiar behaviors (testing phase)...
2017: PloS One
https://www.readbyqxmd.com/read/28636648/cost-effectiveness-of-pazopanib-versus-sunitinib-for-metastatic-renal-cell-carcinoma-in-the-united-kingdom
#11
Jordan Amdahl, Jose Diaz, Arati Sharma, Jinhee Park, David Chandiwana, Thomas E Delea
BACKGROUND: Sunitinib and pazopanib are the only two targeted therapies for the first-line treatment of locally advanced or metastatic renal cell carcinoma (mRCC) recommended by the United Kingdom's National Institute for Health and Care Excellence. Pazopanib demonstrated non-inferior efficacy and a differentiated safety profile versus sunitinib in the phase III COMPARZ trial. The current analysis provides a direct comparison of the cost-effectiveness of pazopanib versus sunitinib from the perspective of the United Kingdom's National Health Service based on data from COMPARZ and other sources...
2017: PloS One
https://www.readbyqxmd.com/read/28636637/plasma-kisspeptin-levels-are-associated-with-insulin-secretion-in-nondiabetic-individuals
#12
Francesco Andreozzi, Gaia Chiara Mannino, Elettra Mancuso, Rosangela Spiga, Francesco Perticone, Giorgio Sesti
To evaluate if plasma kisspeptin concentrations are associated with insulin secretion, as suggested by recent in vitro studies, independently of confounders. 261 nondiabetic subjects were stratified into tertiles according to kisspeptin values. Insulin secretion was assessed using indexes derived from oral glucose tolerance test (OGTT). After adjusting for age, gender, and BMI, subjects in the highest (tertile 3) kisspeptin group exhibited significantly lower values of insulinogenic index, corrected insulin response (CIR30), and Stumvoll indexes for first-phase and second-phase insulin release as compared with low (tertile 1) or intermediate (tertile 2) kisspeptin groups...
2017: PloS One
https://www.readbyqxmd.com/read/28636620/risk-of-ischemic-stroke-after-atrial-fibrillation-diagnosis-a-national-sample-cohort
#13
Mi Kyoung Son, Nam-Kyoo Lim, Hyung Woo Kim, Hyun-Young Park
Atrial fibrillation (AF) is a major risk factor for ischemic stroke and associated with a 5-fold higher risk of stroke. In this retrospective cohort study, the incidence of and risk factors for ischemic stroke in patients with AF were identified. All patients (≥30 years old) without previous stroke who were diagnosed with AF in 2007-2013 were selected from the National Health Insurance Service-National Sample Cohort. To identify factors that influenced ischemic stroke risk, Cox proportional hazard regression analysis was conducted...
2017: PloS One
https://www.readbyqxmd.com/read/28636604/liquid-droplet-formation-by-hp1%C3%AE-suggests-a-role-for-phase-separation-in-heterochromatin
#14
Adam G Larson, Daniel Elnatan, Madeline M Keenen, Michael J Trnka, Jonathan B Johnston, Alma L Burlingame, David A Agard, Sy Redding, Geeta J Narlikar
Gene silencing by heterochromatin is proposed to occur in part as a result of the ability of heterochromatin protein 1 (HP1) proteins to spread across large regions of the genome, compact the underlying chromatin and recruit diverse ligands. Here we identify a new property of the human HP1α protein: the ability to form phase-separated droplets. While unmodified HP1α is soluble, either phosphorylation of its N-terminal extension or DNA binding promotes the formation of phase-separated droplets. Phosphorylation-driven phase separation can be promoted or reversed by specific HP1α ligands...
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28636597/phase-separation-drives-heterochromatin-domain-formation
#15
Amy R Strom, Alexander V Emelyanov, Mustafa Mir, Dmitry V Fyodorov, Xavier Darzacq, Gary H Karpen
Constitutive heterochromatin is an important component of eukaryotic genomes that has essential roles in nuclear architecture, DNA repair and genome stability, and silencing of transposon and gene expression. Heterochromatin is highly enriched for repetitive sequences, and is defined epigenetically by methylation of histone H3 at lysine 9 and recruitment of its binding partner heterochromatin protein 1 (HP1). A prevalent view of heterochromatic silencing is that these and associated factors lead to chromatin compaction, resulting in steric exclusion of regulatory proteins such as RNA polymerase from the underlying DNA...
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28636566/detection-of-muscle-gap-by-l-bia-in-muscle-injuries-clinical-prognosis
#16
L Nescolarde, J Yanguas, J Terricabras, H Lukaski, X Alomar, J Rosell-Ferrer, G Rodas
Sport-related muscle injury classifications are based basically on imaging criteria such as ultrasound (US) and magnetic resonance imaging (MRI) without consensus because of a lack of clinical prognostics for return-to-play (RTP), which is conditioned upon the severity of the injury, and this in turn with the muscle gap (muscular fibers retraction). Recently, Futbol Club Barcelona's medical department proposed a new muscle injury classification in which muscle gap plays an important role, with the drawback that it is not always possible to identify by MRI...
June 21, 2017: Physiological Measurement
https://www.readbyqxmd.com/read/28636538/phase-i-dose-escalation-study-of-the-c-met-tyrosine-kinase-inhibitor-sar125844-in-asian-patients-with-advanced-solid-tumors-including-patients-with-met-amplified-gastric-cancer
#17
Kohei Shitara, Tae Min Kim, Tomoya Yokota, Masahiro Goto, Taroh Satoh, Jin-Hee Ahn, Hyo Song Kim, Sylvie Assadourian, Corinne Gomez, Marzia Harnois, Satoshi Hamauchi, Toshihiro Kudo, Toshihido Doi, Yung-Jue Bang
SAR125844 is a potent and selective inhibitor of the c-Met kinase receptor. This was an open-label, phase I, multicenter, dose-escalation, and dose-expansion trial of SAR125844 in Asian patients with solid tumors, a subgroup of whom had gastric cancer and MET amplification (NCT01657214). SAR125844 was administered by intravenous infusion (260-570 mg/m2) on days 1, 8, 15, and 22 of each 28-day cycle. Objectives were to determine the maximum tolerated dose (MTD) and to evaluate SAR125844 safety and pharmacokinetic profile...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636406/protective-effect-of-intravitreal-administration-of-exosomes-derived-from-mesenchymal-stem-cells-on-retinal-ischemia
#18
Elad Moisseiev, Johnathon D Anderson, Sharon Oltjen, Mayank Goswami, Robert J Zawadzki, Jan A Nolta, Susanna S Park
PURPOSE: Exosomes derived from human mesenchymal stem cells (hMSCs) cultured under hypoxic conditions contain proteins and growth factors that promote angiogenesis. This study investigated the effect of intravitreal administration of these exosomes on retinal ischemia using a murine model. METHODS: Oxygen-induced retinopathy (OIR) was induced by exposing one-week-old male C57BL/6J mice to 5 days of 75% hyperoxic conditioning, and returning to room air. After hyperoxic conditioning, the right eye of each mouse was injected intravitreally with 1 µl saline or exosomes derived from hMSCs and compared to control mice of the same age raised in room air without OIR injected intravitreally with saline...
June 21, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28636388/correlation-between-photoluminescence-and-carrier-transport-and-a-simple-in-situ-passivation-method-for-high-bandgap-hybrid-perovskites
#19
Ryan J Stoddard, Felix T Eickemeyer, John K Katahara, Hugh W Hillhouse
High bandgap mixed-halide hybrid perovskites have higher open-circuit voltage deficits and lower carrier diffusion lengths than their lower-bandgap counterparts. We have developed a Ligand-Assisted Crystallization (LAC) technique that introduces additives in-situ during the solvent wash and developed a new method to dynamically measure the absolute-intensity steady-state photoluminescence and the mean carrier diffusion length simultaneously. The measurements reveal four distinct regimes of material changes and show that photoluminescence brightening often coincides with losses in carrier transport, such as in degradation or phase segregation...
June 21, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28636328/structural-dynamics-of-native-like-ions-in-the-gas-phase-results-from-tandem-ion-mobility-of-cytochrome-c
#20
Samuel J Allen, Rachel M Eaton, Matthew F Bush
Ion mobility (IM) is a gas-phase separation technique that is used to determine the collision cross sections of native-like ions of proteins and protein complexes, which are in turn used as restraints for modeling the structures of those analytes in solution. Here, we evaluate the stability of native-like ions using tandem IM experiments implemented using Structures for Lossless Ion Manipulations (SLIM). In this implementation of tandem IM, ions undergo a first dimension of IM up to a switch that is used to selectively transmit ions of a desired mobility...
June 21, 2017: Analytical Chemistry
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